The objective of this project was to investigate in detail the genetic regulation of immune response to nuclease in mice. This species was chosen since the genome of the mouse is better known than that of other rodents. Staphylococcal nuclease is advantageous as a model immunogen, since: (a) its amino acid sequence and three dimensional structure have been characterized; (b) the immunogen is a protein and appears to be more immunogenic than synthetic polypeptides; (c) a very sensitive enzymatic assay has been developed for detecting antibodies to nuclease; and (d) the molecule can be cleaved into a number of fragments which are capable of binding specific subpopulations of antibodies.